Smoking as a risk factor for lower extremity peripheral artery disease in women compared to men: A systematic review and meta-analysis

Background To investigate whether the relationship between smoking and peripheral artery disease (PAD) differs by sex (PROSPERO CRD42022352318). Methods PubMed, EMBASE, and CINAHL were searched (3 March 2024) for studies reporting associations between smoking and PAD in both sexes, at least adjusted for age. Data were pooled using random effects. Between-study heterogeneity was examined using I2 statistic and Cochran’s Q test. Newcastle-Ottowa Scale was adopted for quality assessment. Results Four cohort studies (n = 2,117,860, 54.4% women) and thirteen cross-sectional studies (n = 230,436, 59.9% women) were included. In cohort studies, former and current smokers had higher risk of PAD than never smokers. Compared to those who never or previously smoked, women current smokers (relative risk (RR) 5.30 (95% confidence interval 3.17, 8.87)) had higher excess risk of PAD than men (RR 3.30 (2.46, 4.42)), women-to-men ratio of RR 1.45 (1.30, 1.62)(I2 = 0%, p = 0.328). In cross-sectional studies, risk of PAD was higher among former and current compared to never smokers, more so in men, women-to-men ratios of odds ratio: 0.64 (0.46, 0.90)(I2 = 30%, p = 0.192), 0.63 (0.50, 0.79)(I2 = 0%, p = 0.594), respectively. For both sexes, risk of PAD was higher among current smokers compared to those who were not currently smoking. Cohort studies and five cross-sectional studies were of good quality, scoring 6 to 8 of a possible maximum 9 points. Eight cross-sectional studies scored 2 to 5. Discussions Further research is required to elucidate sex differences in the relationships between smoking and PAD, as the current evidence is limited and mixed. Tobacco-control programs should consider both sexes.


S3a
Individuals were recruited from selected streets, so it is uncertain how the streets were selected.Sample size was not justified.
China 2008, Zheng 3 ★ ★ ★ ★ Participants were only recruited from hospitals.Sample size was not justified.There were no comparisons between respondents and non-respondents.Socioeconomic status was not adjusted for in the analyses.Assessment of the outcome may be unblind.
China 2023, Yi 4 ★ ★ ★ ★ ★ Sample size was not justified.There were no descriptions of the measurement tool to collect smoking information, so it is unclear how the question was asked.Socioeconomic status was not adjusted for in the analyses.Assessment of the outcome may not be independent and may be unblind.
Finland 2016, Heikkilä 6 ★ ★ ★ ★ Sample size was not justified.There were no comparisons between respondents and non-respondents.There were no descriptions of the measurement tool to collect smoking information, so it is unclear how the question was asked.Socioeconomic status was not adjusted for in the analyses.Assessment of the outcome was not independent and unblind.
Norway 2005, Jensen 7 ★ ★ ★ ★ The average income, the prevalence of higher education, and the prevalence of current smokers are a little lower than the average of Norway.Sample size was not justified.There were no descriptions of the measurement tool to collect smoking information, so it is unclear how the question was asked.Socioeconomic status was not adjusted for in the analyses.

★ ★
Only people aged 65 years old were included.Sample size was not justified.There were no comparisons between respondents and non-respondents.There were no descriptions of the measurement tool to collect smoking information, so it is unclear how the question was asked.Socioeconomic status was not adjusted for in the analyses.Assessment of the outcome may not be independent and may be unblind.Adjustments were different in women and men.Spain 2023, Bermúdez-López 12

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★ ★ ★ ★ Sample size was not justified.There were no comparisons between respondents and non-respondents.Socioeconomic status was not adjusted for in the analyses.Assessment of the outcome may not be independent and may be unblind.
USA 2000, Ness 14 ★ ★ ★ ★ ★ ★ Sample size was not justified.Socioeconomic status was not adjusted for in the analyses.Assessment of the outcome was unblind.
USA 2002, Lamar Welch 15 ★ ★ ★ Sample size was not justified.There were no comparisons between respondents and non-respondents.There were no descriptions of the measurement tool to collect smoking information, so it is unclear how the question was asked.Only the age of the participants was adjusted for in the analyses.Assessment of the outcome may not be independent and may be unblind.
There were no descriptions of the measurement tool to collect smoking information, so it is unclear how the question was asked.Socioeconomic status was not adjusted for in the analyses.
USA 2014, Hiramoto 17 ★ ★ ★ Voluntary screening population of individuals who were willing to self-pay for diagnostic tests, which may not be generalizable to other populations.Sample size was not justified.There were no comparisons between respondents and non-respondents.There were no descriptions of the measurement tool to collect smoking information, so it is unclear how the question was asked.Socioeconomic status was not adjusted for in the analyses.Assessment of the outcome may be unblind.1.
Representativeness of the sample: a) Truly representative of the average in the target population★; b) Somewhat representative of the average in the target population★; c) Selected group of users; d) No description of the sampling strategy.

3.
Non-respondents: a) Comparability between respondents and non-respondents` characteristics is established, and the response rate is satisfactory★; b) The response rate is unsatisfactory, or the comparability between respondents and non-respondents is unsatisfactory; c) No description of the response rate or the characteristics of the responders and the nonresponders.

4.
Ascertainment of the exposure: a) Validated measurement tool★★; b) Non-validated measurement tool, but the tool is available or described★; c) No description of the measurement tool.

5.
The subjects in different outcome groups are comparable, based on the study design or analysis.Confounding factors are controlled.a) The study controls for the most important factor, i.e., socioeconomic status★; b) The study control for any additional factor(s), an additional★.6.
Statistical test: a) The statistical test used to analyze the data is clearly described and appropriate, and the measurement of the association is presented, including confidence intervals or the probability level★; b) The statistical test is not appropriate, not described, or incomplete.
Please refer to S3 File for the refences of studies.
Participants were more likely to live in less socioeconomically deprived areas, and be healthier, than the general population.1. Representativeness of the exposed cohort: a) Truly representative★; b) Somewhat representative★; c) Selected group; d) No description of the derivation of the cohort.2. Selection of the non-exposed cohort: a) Drawn from the same community as the exposed cohort★; b) Drawn from a different source; c) No description of the derivation of the non-exposed cohort.3. Ascertainment of exposure: a) Secure record (e.g., surgical record)★; b) Structured interview★; c) Written self-report; d) No description; e) Other.4. Demonstration that outcome of interest was not present at start of study: a) Yes★; b) No. 5. Comparability of cohorts based on the design or analysis controlled for confounders: a) The study controls for socioeconomic status★; b) The study control for any additional factor(s), an additional★; c) Cohorts are not comparable on the basis of the design or analysis controlled for confounders.6. Assessment of outcome: a) Independent blind assessment★; b) Record linkage★; c) Self-report; d) No description; e) Other.7. Was follow-up long enough for outcomes to occur a) Yes★; b) No. 8. Adequacy of follow-up of cohorts: a) Complete follow up, all subject accounted for★; b) Subjects lost to follow up unlikely to introduce bias, number lost less than or equal to 20% or description of those lost suggested no different from those followed★; c) Follow up rate less than 80% and no description of those lost.Please refer to S3 File for the refences of studies.S3b Table Quality assessment of cross-sectional studies using the Newcastle-

Table
Quality assessment of cohort studies using the Newcastle-Ottawa scale Socioeconomic status was not adjusted for in the analyses.